nach oben

Breast Cancer Research and Treatment

Erschienen in:

29.06.2020 | Clinical trial

Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study

verfasst von: Hadeer G. Khalefa, May A. Shawki, Rasha Aboelhassan, Lamia M. El Wakeel

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of the current study was to evaluate the effect of N-acetylcysteine (NAC) on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients.

Method

A prospective randomized controlled open label study was conducted on 75 breast cancer patients receiving adjuvant paclitaxel 80 mg/m² weekly for 12 weeks. Eligible patients were randomized to either the low dose group; 1200 mg daily NAC, the high dose group; 1200 mg NAC twice daily or the control group; received paclitaxel only. The primary endpoint was the incidence of different grades of PIPN using National Cancer Institute’s common toxicity criteria for adverse event (NCI-CTCAE) while secondary endpoints were the severity of PIPN using modified total neuropathy score (mTNS), quality of life (QOL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX) subscale, serum nerve growth factor (NGF), and serum malondialdehyde (MDA).

Results

At the end of the 12-week period, the incidence of grade (2, 3) peripheral neuropathy was significantly lower in the high dose group (28.6%) compared to the low dose group (61.9%) and the control group (100%), p value < 0.001. A significant improvement in the mTNS and QOL scores was observed after 6 and 12 weeks in the high dose group and the low dose group compared to the control, p value < 0.001. Significantly higher levels of serum NGF in the high dose group and lower level of serum MDA in the high dose and the low dose group were observed.

Conclusion

Oral NAC (1200 mg once and twice daily) might reduce the incidence and severity of PIPN and improve the patients’ QOL.

Trial registry

Clinical Trial.gov registration number: NCT03492047.

Barnard ME, Boeke CE, Tamimi RM (2015) Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta 1856(1):73–85. https://doi.org/10.1016/j.bbcan.2015.06.002 CrossRefPubMed

Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H (2014) Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol 2014:437971. https://doi.org/10.1155/2014/437971 CrossRefPubMedPubMedCentral

Chew HK (2001) Adjuvant therapy for breast cancer: who should get what? West J Med 174(4):284–287. https://doi.org/10.1136/ewjm.174.4.284 CrossRefPubMedPubMedCentral

Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE (2008) Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 358(16):1663–1671. https://doi.org/10.1056/NEJMoa0707056 CrossRefPubMedPubMedCentral

Brami C, Bao T, Deng G (2016) Natural products and complementary therapies for chemotherapy-induced peripheral neuropathy: a systematic review. Crit Rev Oncol Hematol 98:325–334. https://doi.org/10.1016/j.critrevonc.2015.11.014 CrossRefPubMed

Bao T, Basal C, Seluzicki C, Li SQ, Seidman AD, Mao JJ (2016) Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk. Breast Cancer Res Treat 159(2):327–333. https://doi.org/10.1007/s10549-016-3939-0 CrossRefPubMedPubMedCentral

Ewertz M, Qvortrup C, Eckhoff L (2015) Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives. Acta Oncol 54(5):587–591. https://doi.org/10.3109/0284186x.2014.995775 CrossRefPubMed

Bakogeorgos M, Georgoulias V (2017) Risk-reduction and treatment of chemotherapy-induced peripheral neuropathy. Expert Rev Anticancer Ther 17(11):1045–1060. https://doi.org/10.1080/14737140.2017.1374856 CrossRefPubMed

Grisold W, Grisold A (2017) Chemotherapy-induced peripheral neuropathy: limitations in current prophylactic/therapeutic strategies and directions for future research. Curr Med Res Opin 33(7):1291–1292. https://doi.org/10.1080/03007995.2017.1314263 CrossRefPubMed

10.

Carvalho LF, Silva AMF, Carvalho AA (2017) The use of antioxidant agents for chemotherapy-induced peripheral neuropathy treatment in animal models. Clin Exp Pharmacol Physiol 44(10):971–979. https://doi.org/10.1111/1440-1681.12803 CrossRefPubMed

11.

Areti A, Yerra VG, Naidu V, Kumar A (2014) Oxidative stress and nerve damage: role in chemotherapy induced peripheral neuropathy. Redox Biol 2:289–295. https://doi.org/10.1016/j.redox.2014.01.006 CrossRefPubMedPubMedCentral

12.

Ghoreishi Z, Esfahani A, Djazayeri A, Djalali M, Golestan B, Ayromlou H, Hashemzade S, Asghari Jafarabadi M, Montazeri V, Keshavarz SA, Darabi M (2012) Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial. BMC Cancer 12:355. https://doi.org/10.1186/1471-2407-12-355 CrossRefPubMedPubMedCentral

13.

Argyriou AA, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G, Iconomou G, Kalofonos HP (2005) Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology 64(1):26–31. https://doi.org/10.1212/01.wnl.0000148609.35718.7d CrossRefPubMed

14.

Gao W, Zan Y, Wang ZJ, Hu XY, Huang F (2016) Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCepsilon-dependent activation of TRPV1. Acta Pharmacol Sin 37(9):1166–1177. https://doi.org/10.1038/aps.2016.58 CrossRefPubMedPubMedCentral

15.

Griffiths LA, Flatters SJ (2015) Pharmacological modulation of the mitochondrial electron transport chain in paclitaxel-induced painful peripheral neuropathy. J Pain 16(10):981–994. https://doi.org/10.1016/j.jpain.2015.06.008 CrossRefPubMedPubMedCentral

16.

Hershman DL, Lacchetti C, Dworkin RH, Smith EML, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32(18):1941–1967. https://doi.org/10.1200/jco.2013.54.0914 CrossRefPubMed

17.

Li J, Xu L, Deng X, Jiang C, Pan C, Chen L, Han Y, Dai W, Hu L, Zhang G, Cheng Z, Liu W (2016) N-Acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases. Pain 157(8):1711–1723. https://doi.org/10.1097/j.pain.0000000000000575 CrossRefPubMed

18.

Park SA, Choi KS, Bang JH, Huh K, Kim SU (2000) Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand. J Neurochem 75(3):946–953. https://doi.org/10.1046/j.1471-4159.2000.0750946.x CrossRefPubMed

19.

Lin PC, Lee MY, Wang WS, Yen CC, Chao TC, Hsiao LT, Yang MH, Chen PM, Lin KP, Chiou TJ (2006) N-Acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer 14(5):484–487. https://doi.org/10.1007/s00520-006-0018-9 CrossRefPubMed

20.

Coles LD, Tuite PJ, Öz G, Mishra UR, Kartha RV, Sullivan KM, Cloyd JC, Terpstra M (2018) Repeated-dose oral N-acetylcysteine in Parkinson's disease: pharmacokinetics and effect on brain glutathione and oxidative stress. J Clin Pharmacol 58(2):158–167CrossRef

21.

Zhang Y, Gong S, He L, Zhou M, Guo J, Hoke A, Zhu C (2017) Nerve growth factor for neuropathic pain. Cochrane Database Syst Rev 2017(11):CD012800PubMedCentral

22.

Chang DS, Hsu E, Hottinger DG, Cohen SP (2016) Anti-nerve growth factor in pain management: current evidence. J Pain Res 9:373PubMedPubMedCentral

23.

De Santis S, Pace A, Bove L, Cognetti F, Properzi F, Fiore M, Triaca V, Savarese A, Simone MD, Jandolo BJ (2000) Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor. Clin Cancer Res 6(1):90–95PubMed

24.

Smith EM, Beck SL, Cohen J (2008) The total neuropathy score: a tool for measuring chemotherapy-induced peripheral neuropathy. Oncol Nurs Forum 35(1):96–102. https://doi.org/10.1188/08.onf.96-102 CrossRefPubMed

25.

Wampler MA, Miaskowski C, Hamel K, Byl N, Rugo H, Topp KS (2006) The modified total neuropathy score: a clinically feasible and valid measure of taxane-induced peripheral neuropathy in women with breast cancer. J Support Oncol 4(8):W9–W16

26.

Huang HQ, Brady MF, Cella D, Fleming G (2007) Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer 17(2):387–393. https://doi.org/10.1111/j.1525-1438.2007.00794.x CrossRefPubMed

27.

Calhoun EA, Welshman E, Chang C-H, Lurain J, Fishman D, Hunt T, Cella DJ (2003) Psychometric evaluation of the functional assessment of cancer therapy/gynecologic oncology group—neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 13(6):741–748PubMed

28.

Tsikas D, Rothmann S, Schneider JY, Suchy M-T, Trettin A, Modun D, Stuke N, Maassen N, Frölich JC (2016) Development, validation and biomedical applications of stable-isotope dilution GC–MS and GC–MS/MS techniques for circulating malondialdehyde (MDA) after pentafluorobenzyl bromide derivatization: MDA as a biomarker of oxidative stress and its relation to 15 (S)-8-iso-prostaglandin F2α and nitric oxide (NO). J Chromatogr 1019:95–111

29.

Singh Z, Karthigesu IP, Singh P, Rupinder KJ (2014) Use of malondialdehyde as a biomarker for assessing oxidative stress in different disease pathologies: a review. Iran J Public Health 43(3):7–16

30.

Carr AJ, Higginson IJ (2001) Are quality of life measures patient centred? BMJ 322(7298):1357–1360. https://doi.org/10.1136/bmj.322.7298.1357 CrossRefPubMedPubMedCentral

31.

Tofthagen C, Visovsky C, Dominic S, McMillan S (2019) Neuropathic symptoms, physical and emotional well-being, and quality of life at the end of life. Support Care Cancer 27(9):3357–3364. https://doi.org/10.1007/s00520-018-4627-x CrossRefPubMed

32.

Cella D, Peterman A, Hudgens S, Webster K, Socinski MA (2003) Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane). Cancer 98(4):822–831. https://doi.org/10.1002/cncr.11578 CrossRefPubMed

33.

Crevenna R, Ashbury FD (2018) Physical interventions for patients suffering from chemotherapy-induced polyneuropathy. Support Care Cancer 26(4):1017–1018. https://doi.org/10.1007/s00520-018-4071-y CrossRefPubMed

34.

Youk J, Kim YS, Lim JA, Shin DY, Koh Y, Lee ST, Kim I (2017) Depletion of nerve growth factor in chemotherapy-induced peripheral neuropathy associated with hematologic malignancies. PLoS ONE 12(8):e0183491. https://doi.org/10.1371/journal.pone.0183491 CrossRefPubMedPubMedCentral

35.

Decroli E, Manaf A, Syahbuddin S, Syafrita Y, Dillasamola D (2019) The correlation between malondialdehyde and nerve growth factor serum level with diabetic peripheral neuropathy score. Open Access Maced J Med Sci 7(1):103CrossRef

36.

Cavaletti G, Bogliun G, Marzorati L, Zincone A, Piatti M, Colombo N, Franchi D, La Presa MT, Lissoni A, Buda A, Fei F, Cundari S, Zanna C (2004) Early predictors of peripheral neurotoxicity in cisplatin and paclitaxel combination chemotherapy. Ann Oncol 15(9):1439–1442. https://doi.org/10.1093/annonc/mdh348 CrossRefPubMed

37.

Binder CJ (2017) Lipid modification and lipid peroxidation products in innate immunity and inflammation. Biochim Biophys Acta Mol Cell Biol Lipids 1862(4):369–370. https://doi.org/10.1016/j.bbalip.2017.01.006 CrossRefPubMed

38.

Kim ST, Chung YH, Lee HS, Chung SJ, Lee JH, Sohn UD, Shin YK, Park ES, Kim HC, Bang JS, Jeong JH (2015) Protective effects of phosphatidylcholine on oxaliplatin-induced neuropathy in rats. Life Sci 130:81–87. https://doi.org/10.1016/j.lfs.2015.03.013 CrossRefPubMed

Titel: Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study
verfasst von: Hadeer G. Khalefa
May A. Shawki
Rasha Aboelhassan
Lamia M. El Wakeel
Publikationsdatum: 29.06.2020
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05762-8

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study

Abstract

Purpose

Method

Results

Conclusion

Trial registry

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Method

Results

Conclusion

Trial registry

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2020

Prognostic potential of automated Ki67 evaluation in breast cancer: different hot spot definitions versus true global score

A case for Tamoxifen with ovarian function suppression

Activation of mitochondrial unfolded protein response is associated with Her2-overexpression breast cancer

Cardiovascular mortality and morbidity burden in successive and age pre-stratified case–control cohorts of breast cancer women. A population-based study

Factors influencing adherence to adjuvant endocrine therapy in breast cancer-treated women: using real-world data to inform a switch from acute to chronic disease management

Optimal breast reconstruction type for patients treated with neoadjuvant chemotherapy, mastectomy followed by radiation therapy

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie